View More View Less
  • 1 Debreceni Egyetem, Általános Orvostudományi Kar, Belgyógyászati Klinika, Reumatológia, Debrecen, Nagyerdei krt. 98., 4032
  • | 2 Országos Korányi Pulmonológiai Intézet, Budapest
  • | 3 Semmelweis Egyetem, Általános Orvostudományi Kar, II. Gyermekgyógyászati Klinika, Budapest
  • | 4 Debreceni Egyetem, Általános Orvostudományi Kar, Aneszteziológiai és Intenzív Terápiás Klinika, Debrecen
  • | 5 Semmelweis Egyetem, Általános Orvostudományi Kar, Pulmonológiai Klinika, Budapest
  • | 6 Debreceni Egyetem, Általános Orvostudományi Kar, Infektológiai Klinika, Debrecen
  • | 7 Dél-pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, Budapest
Open access

Összefoglaló. Az új típusú koronavírus-fertőzés (COVID–19) nagy terhet ró az egészségügyi ellátórendszerre és a társadalomra. A betegségnek három nagy szakasza van, melyek alapvetően meghatározzák a kezelést. Az I–IIA fázisban az antivirális, míg a IIB–III. fázisban a gyulladásgátló kezelés áll előtérben, melyhez intenzív terápiás, szupportív kezelés csatlakozik. A jelen ajánlás kizárólag a gyógyszeres kezelésre vonatkozik, és a rendelkezésre álló bizonyítékok alapján foglalja össze a terápiás lehetőségeket. Emellett egy javasolt kezelési algoritmust is tartalmaz. Orv Hetil. 2021; 162(17): 643–651.

Summary. The novel coronavirus infection (COVID-19) places a heavy burden on the health care system and our society. There are three major stages in the disease that fundamentally determine treatment approaches. Phases I–IIA require primarily antiviral treatment. In phases IIB–III, anti-inflammatory treatment is needed accompanied by intensive and supportive care. This recommendation applies only to pharmacotherapy and summarizes the therapeutic options based on the available evidence. It also includes a proposed treatment algorithm. Orv Hetil. 2021; 162(17): 643–651.

  • 1

    Szekanecz Z, Bálint P, Balog A, et al. Immunologic and rheumatologic aspects of COVID-19. [A COVID–19 fertőzés immunológiai és reumatológiai vonatkozásai.] Immunol Szle. 2020; 12(2): 5–17. [Hungarian]

  • 2

    Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020; 39: 405–407.

  • 3

    Handbook of prevention and therapy of novel coronavirus (SARS-CoV-2) infection identified in 2020. [A 2020. évben azonosított új koronavírus (SARS-CoV-2) okozta fertőzések (COVID–19) megelőzésének és terápiájának kézikönyve. 3. kiadás.] Emberi Erőforrások Minisztériuma, Budapest, 2020. december 18. [Hungarian]

  • 4

    World Health Organization. COVID-19 clinical management: living guidance. WHO, Geneva, Jan 25, 2021. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [accessed: ].

  • 5

    Szekanecz Z, Bálint P, Balog A, et al. COVID-19: cytokine storm and beyond. [COVID-19: a citokinviharon innen és túl ...] Immunol Szle. 2020; 12(4): 5–15. [Hungarian]

  • 6

    Webb BJ, Peltan ID, Jensen P, et al. Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study. Lancet Rheumatol. 2020; 2: e754–e763

  • 7

    Gandhi RT, Lynch JB, Del Rio C. Mild or moderate COVID-19. N Engl J Med. 2020; 383: 1757–1766.

  • 8

    Sciascia S, Apra F, Baffa A, et al. Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin Exp Rheumatol. 2020; 38: 529–532.

  • 9

    Mojtabavi H, Saghazadeh A, Rezaei N. Interleukin-6 and severe COVID-19: a systematic review and meta-analysis. Eur Cytokine Netw. 2020; 31: 44–49.

  • 10

    Mudd PA, Crawford JC, Turner JS, et al. Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm. Sci Adv. 2020; 6: eabe3024.

  • 11

    Alunno A, Najm A, Machado PM, et al. EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19. Ann Rheum Dis. 2021 Feb 5. [Online ahead of print]

  • 12

    Kox M, Waalders NJB, Kooistra EJ, et al. Cytokine levels in critically ill patients with COVID-19 and other conditions. JAMA 2020; 324: 1525–1527.

  • 13

    Martinez MA. Clinical trials of repurposed antivirals for SARS-CoV-2. Antimicrob Agents Chemother. 2020; 64: e01101–20.

  • 14

    Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19 – final report. N Engl J Med. 2020; 383: 1813–1826.

  • 15

    RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2020; 396: 1345–1352.

  • 16

    Consortium WHOST, Pan H, Peto R, et al. Repurposed antiviral drugs for COVID-19 – interim WHO Solidarity Trial results. N Engl J Med. 2021; 384: 497–511.

  • 17

    U.S. Food and Drug Administration. Emergency use authorization. FDA, White Oak, MD, 2020. Available from: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization [accessed: March 3, 2021].

  • 18

    Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with COVID-19. N Engl J Med. 2021; 384: 229–237.

  • 19

    Gottlieb RL, Nirula A, Chen P, et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA 2021; 325: 632–644.

  • 20

    An EUA for bamlanivimab. A monoclonal antibody for COVID-19. Med Lett Drugs Ther. 2020; 62: 185–186.

  • 21

    Bloch EM, Shoham S, Casadevall A, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest. 2020; 130: 2757–2765.

  • 22

    Joyner MJ, Carter RE, Senefeld JW, et al. Convalescent plasma antibody levels and the risk of death from COVID-19. N Engl J Med. 2021; 384: 1015–1027.

  • 23

    Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA 2020; 117: 9490–9496.

  • 24

    Libster R, Perez Marc G, Wappner D, et al. Early high-titer plasma therapy to prevent severe COVID-19 in older adults. N Engl J Med. 2021; 384: 610–618.

  • 25

    Simonovich VA, Burgos Pratx LD, Scibona P, et al. A randomized trial of convalescent plasma in COVID-19 severe pneumonia. N Engl J Med. 2021; 384: 619–629.

  • 26

    Ferro F, Elefante E, Baldini C, et al. COVID-19: the new challenge for rheumatologists. Clin Exp Rheumatol. 2020; 38: 175–180.

  • 27

    Akiyama S, Hamdeh S, Micic D, et al. Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis. Ann Rheum Dis. 2021; 80: 384–391.

  • 28

    RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with COVID-19. Preliminary report. N Engl J Med. 2020; 384: 693–704.

  • 29

    Ramiro S, Mostard RLM, Magro-Checa C, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Ann Rheum Dis. 2020; 79: 1143–1151.

  • 30

    Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA 2020; 117: 10970–10975.

  • 31

    Gordon AC, Mouncey PR, Al-Beidh F, et al. Interleukin-6 receptor antagonists in critically ill patients with COVID-19. Preliminary report. N Engl J Med. 2021 Feb 25. . [Epub ahead of print]

    • Crossref
    • Export Citation
  • 32

    Klopfenstein T, Zayet S, Lohse A, et al. Impact of tocilizumab on mortality and/or invasive mechanical ventilation requirement in a cohort of 206 COVID-19 patients. Int J Infect Dis. 2020; 99: 491–495.

  • 33

    Lakatos B, Gopcsa L, Gondos E, et al. Anti-cytokine therapy in novel coronavirus disease (COVID-19). The first administration of tocilizumab in Hungary at a department of infectology. [Citokinellenes terápia az új típusú koronavírus okozta megbetegedés (COVID–19) kezelésében – tocilizumab elsőként való alkalmazása egy hazai infektológiai osztályon.] Orv Hetil. 2020; 161: 1070–1077. [Hungarian]

  • 34

    Gupta S, Wang W, Hayek SS, et al. Association between early treatment with tocilizumab and mortality among critically ill patients with COVID-19. JAMA Intern Med. 2021; 181: 41–51.

  • 35

    RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial. medRXiv 2021 Feb 11. [.]

    • Crossref
    • Export Citation
  • 36

    F. Hoffmann-La Roche Ltd. Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia (press release). 29 July 2020. Available from: https://www.roche.com/investors/updates/inv-update-2020-07-29.htm [accessed: March 3, 2021].

  • 37

    Furlow B. COVACTA trial raises questions about tocilizumab’s benefit in COVID-19. Lancet Rheumatol. 2020; 2: e592.

  • 38

    Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with COVID-19. N Engl J Med. 2020; 383: 2333–2344.

  • 39

    Hermine O, Mariette X, Tharaux PL, et al. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med. 2021; 181: 32–40.

  • 40

    Salvarani C, Dolci G, Massari M, et al. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA Intern Med. 2021; 181: 24–31.

  • 41

    Winthrop KL, Yamanaka H, Valdez H, et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014; 66: 2675–2684.

  • 42

    Bronte V, Ugel S, Tinazzi E, et al. Baricitinib restrains the immune dysregulation in patients with severe COVID-19. J Clin Invest. 2020; 130: 6409–6416.

  • 43

    Tsai YC, Tsai TF. Oral disease-modifying antirheumatic drugs and immunosuppressants with antiviral potential, including SARS-CoV-2 infection: a review. Ther Adv Musculoskelet Dis. 2020; 12: 1759720X20947296.

  • 44

    Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021; 384: 795–807.

  • 45

    U.S. Food and Drug Administration. Coronavirus (COVID-19) update: FDA authorizes drug combination for treatment of COVID-19. FDA, White Oak, MD, Nov 19, 2020. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-combination-treatment-covid-19 [accessed: March 3, 2021].

  • 46

    Merrill JT, Erkan D, Winakur J, Jet al. Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications. Nat Rev Rheumatol. 2020; 16: 581–589.

  • 47

    Langer-Gould A, Smith JB, Gonzales EG, et al. Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab. Int J Infect Dis. 2020; 99: 291–297.

  • 48

    Pontali E, Volpi S, Signori A, et al. Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia. J Allergy Clin Immunol. 2021 Feb 6. S0091-6749(21)00171-8. . [Online ahead of print]

    • Crossref
    • Export Citation
  • 49

    CORIMUNO-19 Collaborative Group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. Lancet Respir Med. 2021; 9: 295–304.

  • 50

    Landi L, Ravaglia C, Russo E, et al. Blockage of interleukin-1β with canakinumab in patients with COVID-19. Sci Rep. 2020; 10: 21775.

  • 51

    Della-Torre E, Campochiaro C, Cavalli G, et al. Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study. Ann Rheum Dis. 2020; 79: 1277–1285.

  • 52

    Sanofi. Sanofi provides update on Kevzara® (sarilumab) phase 3 trial in severe and critically ill COVID-19 patients outside the U.S. (press release). Sep 1, 2020. Available from: https://www.sanofi.com/en/media-room/press-releases/2020/2020-09-01-07-00-00 [accessed: March 3, 2021].

  • 53

    Innes AJ, Cook LB, Marks S, et al. Ruxolitinib for tocilizumab-refractory severe COVID-19 infection. Br J Haematol. 2020; 190: e198–e200.

  • 54

    Cao Y, Wei J, Zou L, et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020; 146: 137–146.e3.

  • 55

    Gharebaghi N, Nejadrahim R, Mousavi SJ, et al. The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial. BMC Infect Dis. 2020; 20: 786.

  • 56

    Tabarsi P, Barati S, Jamaati H, et al. Evaluating the effects of intravenous immunoglobulin (IVIg) on the management of severe COVID-19 cases: a randomized controlled trial. Int Immunopharmacol. 2021; 90: 107205.

  • 57

    RECOVERY Collaborative Group. Effect of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020; 383: 2030–2040.

  • 58

    RECOVERY Collaborative Group. Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397: 605–612.

  • 59

    Marshall M. The lasting misery of coronavirus long-haulers. Nature 2020; 585: 339–341.

  • 60

    Greenhalgh T, Knight M, A’Court C, et al. Management of post-acute COVID-19 in primary care. BMJ 2020; 370: m3026.

  • 61

    Galluccio F, Ergonenc T, Garcia Martos A, et al. Treatment algorithm for COVID-19: a multidisciplinary point of view. Clin Rheumatol. 2020; 39: 2077–2084.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1435 1435 225
PDF Downloads 2446 2446 393